What is multiple myeloma? (Drs Landgren and Gertz)

So, what is multiple myeloma? Multiple myeloma is a blood disorder that is thought to originate from plasma cells. It's a disease that happens in about 30,000 Americans every year. There are more than 120,000 Americans living with the disease. It is a disease that can present itself in very many different ways. Some patients can have the disease without being really that sick, and some patients, unfortunately, can have a very rapid disease process. The disease can manifest in fractures; it can manifest in high levels of calcium in the body that makes the person very sick, and it can result in acute kidney failure that can be due to both the calcium and protein that the disease also leaks out in the blood.

When we study the disease in the laboratory and we have started using very sophisticated assays when we do profiling of the DNA and the RNA, we see that every patient with myeloma has very many alterations genomically. We have seen that there are many, many parallel subtypes of myeloma going on at the same time in that same patient, and it's different across different patients. I do think when we treat patients with multiple myeloma with all best treatments, I strongly believe that we probably cure the patient from some of these subsets of the disease, but there are some subsets of the disease that we don't get rid of, unfortunately, and we are working on that. So, when we follow patients over time, when the disease comes back, those subsets can come back, and they can be more aggressive. It may not happen at the first relapse, but it could happen at later relapses.

Multiple myeloma is found more frequently in older individuals. The average age of diagnosis is 70 years old, and people of African descent are two to three times more likely to develop the disease than Caucasians. There are two precursor conditions that can develop into active myeloma: one is called monoclonal gammopathy of undetermined significance, and the other is called smoldering myeloma, also known as asymptomatic myeloma.

Now, let's hear from Dr. Gertz about how multiple myeloma develops: Three major crops in the garden. About 20% of the acreage in that bone marrow garden is given over to red blood cell production, the cells that carry oxygen, give you your energy. You don't have enough then you're called anemic. 60 percent are infection-fighting white blood cells that protect you against the development of infection. About ten percent are given over to the production of blood-clotting cells, and they're about ten percent that are boutique crops that go by a whole host of different names, but they're not relevant to our discussion. But in every normal bone marrow, 1% of that acreage, 1% ourselves called plasma cells, their protein-producing cells that help protect your body's immunity, and their protein production of those plasma cells it's an important concept to understand. You get a flu shot, you plasma cells will start making antibody proteins to protect you. Your skin, your knee when you're four, you're gonna have a plasma saw making antibodies to the exposed contaminants. So, that's normal, and if you look at the bone marrow in those proportions: sixty, twenty, ten, and plasma cells one, you guess what it is at age four, fourteen, twenty-four, eighty-four, those proportions are very, very tightly controlled, no variation.

Unfortunately, sometimes malignancy develops and the characteristic of malignancy, of course, is uncontrolled growth of cells. One of those plasma cells loses those growth regulatory controls, usually acquire genetic changes occur, and it develops a growth advantage. It starts growing in the garden, that 1% of the acreage, and it'll grow and it'll grow. By definition, if the acreage is greater than 10% plasma cells, that's defined as multiple myeloma. The average patient with multiple myeloma at the time of diagnosis, that acreage is about 40% on average. At the time it's diagnosed, we can go up to a hundred percent.

The consequences of the development of these weeds in the garden are threefold. The first one is, as the weeds grow, these are choking off all the normal plants so that they're no longer able to germinate correctly. The first consequence of that is it chokes off the red blood cell plants in that garden, and that consequence is a reduction in production of red cells, a drop in the blood hemoglobin level. You are anemic. So, for some patients, 70% at the time of diagnosis, weak, tired, exertional shortness of breath, can't climb the stairs anymore, and the evaluation to the doctors: "I'm anemic."

Number two is that these weeds don't just stay in the garden, they actually begin to erode into the casing of the garden. Well, what's the casing of the garden I'm talking about? Well, that's the surrounding bone. You go to the supermarket to get a bone for soup, you know the bone's made out of two separate parts. There's a thick outer white shell on the bone which allows you to actually jump on the bone, you wouldn't break it, and then, then there's that kind of spongy core that's kind of brown and kind of webby, and then of course is the bone marrow. In a freshness or an animal, it's bright red because it's the same color as blood because that's where the blood is produced. What ends up happening as these weeds grow, they'll begin to invade the casing, that cortical bone, and start to dissolve and damage it. And that weakens the bone because as you know, bone is rock-hard, but clusters of myeloma cells actually have the consistency of raw liver. And so, you replace bone with raw liver death, bone is weaker, and what will happen is, particularly in bones that are under a lot of weight stress, which is spine and ribs, they're prone to fractures.

Myeloma patients can additionally get more frequent infections like pneumonia or the flu because myeloma cells crowd out infection-fighting cells that normally fight off diseases. This leaves your immune system weakened.

What is the future of myeloma treatment? We need to better understand all these processes work. We need to develop better drugs, and we need to absolutely develop better tools for tracking of the disease. I started treating patients quite a few years ago with myeloma. At that time, the average survival was only one to three years, and I was advised by senior doctors and mentors that I should probably not focus on myeloma because it was really a disease where there has not been a lot of development. I thought that was a great opportunity, and I'm very glad I took that path. It has been just amazing to see during the past few years how survival has improved.

I think we are now at the point for the average patient that is offered optimal therapy, probably has an overall survival. I would guess on average ten to twenty years. And I also know that there are very many new drugs in development, so I think doing those coming 1020 years there will be very many new drugs that will come to clinic. So I think that could be patients as would live with the disease. I live a very very long life and also with very good quality of life. It should be said that that could be rough spots because we don't have yet the cure, and that's what we need to focus on trying to come up with that.